Enoxaparin Sodium Injection

Included as part of the PRECAUTIONS section.

Accidental overdosage following administration of Lovenox may lead to hemorrhagic complications. Injected Lovenox may be largely neutralized by the slow IV injection of protamine sulfate (1% solution). The dose of protamine sulfate should be equal to the dose of Lovenox injected: 1 mg protamine sulfate should be administered to neutralize 1 mg Lovenox, if enoxaparin sodium was administered in the previous 8 hours. An infusion of 0.5 mg protamine per 1 mg of enoxaparin sodium may be administered if enoxaparin sodium was administered greater than 8 hours previous to the protamine administration, or if it has been determined that a second dose of protamine is required. The second infusion of 0.5 mg protamine sulfate per 1 mg of Lovenox may be administered if the aPTT measured 2 to 4 hours after the first infusion remains prolonged.

If at least 12 hours have elapsed since the last enoxaparin sodium injection, protamine administration may not be required; however, even with higher doses of protamine, the aPTT may remain more prolonged than following administration of heparin. In all cases, the anti-Factor Xa activity is never completely neutralized (maximum about 60%). Particular care should be taken to avoid overdosage with protamine sulfate. Administration of protamine sulfate can cause severe hypotensive and anaphylactoid reactions. Because fatal reactions, often resembling anaphylaxis, have been reported with protamine sulfate, it should be given only when resuscitation techniques and treatment of anaphylactic shock are readily available. For additional information consult the labeling of protamine sulfate injection products.

Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

All patients should be evaluated for a bleeding disorder before administration of Enoxaparin Sodium Injection, unless the medication is needed urgently. Since coagulation parameters are unsuitable for monitoring Enoxaparin Sodium Injection activity, routine monitoring of coagulation parameters is not required [see Warnings and Precautions (5.9)].

For subcutaneous use, Enoxaparin Sodium Injection should not be mixed with other injections or infusions.

For intravenous use (i.e., for treatment of acute STEMI), Enoxaparin Sodium Injection can be mixed with normal saline solution (0.9%) or 5% dextrose in water.

Enoxaparin Sodium Injection is not intended for intramuscular administration.

Adult Dosage

Abdominal Surgery: In patients undergoing abdominal surgery who are at risk for thromboembolic complications, the recommended dose of Enoxaparin Sodium Injection is 40 mg once a day administered by SC injection with the initial dose given 2 hours prior to surgery. The usual duration of administration is 7 to 10 days; up to 12 days administration has been administered in clinical trials.

Hip or Knee Replacement Surgery: In patients undergoing hip or knee replacement surgery, the recommended dose of Enoxaparin Sodium Injection is 30 mg every 12 hours administered by SC injection. Provided that hemostasis has been established, the initial dose should be given 12 to 24 hours after surgery. For hip replacement surgery, a dose of 40 mg once a day SC, given initially 12 (±3) hours prior to surgery, may be considered. Following the initial phase of thromboprophylaxis in hip replacement surgery patients, it is recommended that continued prophylaxis with Enoxaparin Sodium Injection 40 mg once a day be administered by SC injection for 3 weeks. The usual duration of administration is 7 to 10 days; up to 14 days administration has been administered in clinical trials.

Medical Patients During Acute Illness: In medical patients at risk for thromboembolic complications due to severely restricted mobility during acute illness, the recommended dose of Enoxaparin Sodium Injection is 40 mg once a day administered by SC injection. The usual duration of administration is 6 to 11 days; up to 14 days of Enoxaparin Sodium Injection has been administered in the controlled clinical trial.

Treatment of Deep Vein Thrombosis with or without Pulmonary Embolism: In outpatient treatment, patients with acute deep vein thrombosis without pulmonary embolism who can be treated at home, the recommended dose of Enoxaparin Sodium Injection is 1 mg/kg every 12 hours administered SC. In inpatient (hospital) treatment, patients with acute deep vein thrombosis with pulmonary embolism or patients with acute deep vein thrombosis without pulmonary embolism (who are not candidates for outpatient treatment), the recommended dose of Enoxaparin Sodium Injection is 1 mg/kg every 12 hours administered SC or 1.5 mg/kg once a day administered SC at the same time every day. In both outpatient and inpatient (hospital) treatments, warfarin sodium therapy should be initiated when appropriate (usually within 72 hours of Enoxaparin Sodium Injection). Enoxaparin Sodium Injection should be continued for a minimum of 5 days and until a therapeutic oral anticoagulant effect has been achieved (International Normalization Ratio 2.0 to 3.0). The average duration of administration is 7 days; up to 17 days of Enoxaparin Sodium Injection administration has been administered in controlled clinical trials.

Unstable Angina and Non-Q-Wave Myocardial Infarction: In patients with unstable angina or non-Q-wave myocardial infarction, the recommended dose of Enoxaparin Sodium Injection is 1 mg/kg administered SC every 12 hours in conjunction with oral aspirin therapy (100 to 325 mg once daily). Treatment with Enoxaparin Sodium Injection should be prescribed for a minimum of 2 days and continued until clinical stabilization. The usual duration of treatment is 2 to 8 days; up to 12.5 days of Enoxaparin Sodium Injection has been administered in clinical trials [see Warnings and Precautions (5.2) and Clinical Studies (14.5)].

Treatment of Acute ST-Segment Elevation Myocardial Infarction:

In patients with acute ST-segment elevation myocardial infarction, the recommended dose of Enoxaparin Sodium Injection is a single IV bolus of 30 mg plus a 1 mg/kg SC dose followed by 1 mg/kg administered SC every 12 hours (maximum 100 mg for the first two doses only, followed by 1 mg/kg dosing for the remaining doses). Dosage adjustments are recommended in patients ≥75 years of age [see Dosage and Administration (2.3)]. All patients should receive aspirin as soon as they are identified as having STEMI and maintained with 75 to 325 mg once daily unless contraindicated.

When administered in conjunction with a thrombolytic (fibrin-specific or non-fibrin specific), Enoxaparin Sodium Injection should be given between 15 minutes before and 30 minutes after the start of fibrinolytic therapy. In the pivotal clinical study, the Enoxaparin Sodium Injection treatment duration was 8 days or until hospital discharge, whichever came first. An optimal duration of treatment is not known, but it is likely to be longer than 8 days.

For patients managed with percutaneous coronary intervention (PCI): If the last Enoxaparin Sodium Injection SC administration was given less than 8 hours before balloon inflation, no additional dosing is needed. If the last Enoxaparin Sodium Injection SC administration was given more than 8 hours before balloon inflation, an IV bolus of 0.3 mg/kg of Enoxaparin Sodium Injection should be administered [see Warnings and Precautions (5.2)].

Renal Impairment

Although no dose adjustment is recommended in patients with moderate (creatinine clearance 30–50 mL/min) and mild (creatinine clearance 50–80 mL/min) renal impairment, all such patients should be observed carefully for signs and symptoms of bleeding.

The recommended prophylaxis and treatment dosage regimens for patients with severe renal impairment (creatinine clearance <30 mL/min) are described in Table 1 [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

Geriatric Patients with Acute ST-Segment Elevation Myocardial Infarction

For treatment of acute ST-segment elevation myocardial infarction in geriatric patients ≥75 years of age, do not use an initial IV bolus. Initiate dosing with 0.75 mg/kg SC every 12 hours (maximum 75 mg for the first two doses only, followed by 0.75 mg/kg dosing for the remaining doses) [see Use in Specific Populations (8.5) and Clinical Phamacology (12.3)].

No dose adjustment is necessary for other indications in geriatric patients unless kidney function is impaired [see Dosage and Administration (2.2)].

Administration

Enoxaparin Sodium Injection is a clear, colorless to pale yellow sterile solution, and as with other parenteral drug products, should be inspected visually for particulate matter and discoloration prior to administration.

Enoxaparin Sodium Injection must not be administered by intramuscular injection.

Enoxaparin Sodium Injection is intended for use under the guidance of a physician.

For subcutaneous administration, patients may self-inject only if their physicians determine that it is appropriate and with medical follow-up, as necessary. Proper training in subcutaneous injection technique (with or without the assistance of an injection device) should be provided.

Subcutaneous Injection Technique: Patients should be lying down and Enoxaparin Sodium Injection administered by deep SC injection. To avoid the loss of drug when using the 30 and 40 mg prefilled syringes, do not expel the air bubble from the syringe before the injection. Administration should be alternated between the left and right anterolateral and left and right posterolateral abdominal wall. The whole length of the needle should be introduced into a skin fold held between the thumb and forefinger; the skin fold should be held throughout the injection. To minimize bruising, do not rub the injection site after completion of the injection.

Enoxaparin Sodium Injection prefilled syringes and graduated prefilled syringes are for single, one-time use only and are available with a system that shields the needle after injection.

Remove the prefilled syringe from the blister packaging by peeling at the arrow as directed on the blister. Do not remove by pulling on the plunger as this may damage the syringe.

• Remove needle cover by pulling straight off of needle (see Figure 1). If adjusting the dose is required, the adjustment must be done prior to injecting the prescribed dose into the patient.
  
• See Administration: Subcutaneous Injection Technique for a description of the Standard Protocol for administration.
  
• Depress the plunger while grasping the finger flange until the entire dose has been given. The Passive needle guard should not activate unless the entire dose has been given.
  
• Remove needle from patient, then let go of the plunger and allow syringe to move up until the entire needle is guarded.
  
• Dispose of syringe/needle guard assembly in approved sharps container.
  

NOTE:

• The safety system should only activate once the syringe has been emptied.
• Activation of the safety system must be done only after removing the needle from the patient's skin.
• Do not replace the needle shield after injection.
• The safety system should not be sterilized.

Activation of the safety system may cause minimal splatter of fluid. For optimal safety activate the system while orienting it downwards away from yourself and others.

Intravenous (Bolus) Injection Technique

For intravenous injection, the multiple-dose vial should be used. Enoxaparin Sodium Injection should be administered through an intravenous line. Enoxaparin Sodium Injection should not be mixed or co-administered with other medications. To avoid the possible mixture of Enoxaparin Sodium Injection with other drugs, the intravenous access chosen should be flushed with a sufficient amount of saline or dextrose solution prior to and following the intravenous bolus administration of Enoxaparin Sodium Injection to clear the port of drug. Enoxaparin Sodium Injection may be safely administered with normal saline solution (0.9%) or 5% dextrose in water.

Whenever possible, agents which may enhance the risk of hemorrhage should be discontinued prior to initiation of Enoxaparin Sodium Injection therapy. These agents include medications such as: anticoagulants, platelet inhibitors including acetylsalicylic acid, salicylates, NSAIDs (including ketorolac tromethamine), dipyridamole, or sulfinpyrazone. If co-administration is essential, conduct close clinical and laboratory monitoring [see Warnings and Precautions (5.9)].

Accidental overdosage following administration of Enoxaparin Sodium Injection may lead to hemorrhagic complications. Injected Enoxaparin Sodium Injection may be largely neutralized by the slow IV injection of protamine sulfate (1% solution). The dose of protamine sulfate should be equal to the dose of Enoxaparin Sodium Injection injected: 1 mg protamine sulfate should be administered to neutralize 1 mg Enoxaparin Sodium Injection, if enoxaparin sodium was administered in the previous 8 hours. An infusion of 0.5 mg protamine per 1 mg of enoxaparin sodium may be administered if enoxaparin sodium was administered greater than 8 hours previous to the protamine administration, or if it has been determined that a second dose of protamine is required. The second infusion of 0.5 mg protamine sulfate per 1 mg of Enoxaparin Sodium Injection may be administered if the aPTT measured 2 to 4 hours after the first infusion remains prolonged.

If at least 12 hours have elapsed since the last Enoxaparin Sodium Injection, protamine administration may not be required; however, even with higher doses of protamine, the aPTT may remain more prolonged than following administration of heparin. In all cases, the anti-Factor Xa activity is never completely neutralized (maximum about 60%). Particular care should be taken to avoid overdosage with protamine sulfate. Administration of protamine sulfate can cause severe hypotensive and anaphylactoid reactions. Because fatal reactions, often resembling anaphylaxis, have been reported with protamine sulfate, it should be given only when resuscitation techniques and treatment of anaphylactic shock are readily available. For additional information consult the labeling of protamine sulfate injection products.

Enoxaparin Sodium Injection is a sterile aqueous solution containing enoxaparin sodium, a low molecular weight heparin. The pH of the injection is 5.5 to 7.5.

Enoxaparin sodium is obtained by alkaline depolymerization of heparin benzyl ester derived from porcine intestinal mucosa. Its structure is characterized by a 2-O-sulfo-4-enepyranosuronic acid group at the non-reducing end and a 2-N,6-O-disulfo-D-glucosamine at the reducing end of the chain. About 20% (ranging between 15% and 25%) of the enoxaparin structure contains an 1,6 anhydro derivative on the reducing end of the polysaccharide chain. The drug substance is the sodium salt. The average molecular weight is about 4500 daltons. The molecular weight distribution is:

Enoxaparin Sodium Injection 100 mg/mL Concentration contains 10 mg enoxaparin sodium (approximate anti-Factor Xa activity of 1000 IU [with reference to the W.H.O. Second International Low Molecular Weight Heparin Reference Standard]) per 0.1 mL Water for Injection.

Enoxaparin Sodium Injection 150 mg/mL Concentration contains 15 mg enoxaparin sodium (approximate anti-Factor Xa activity of 1500 IU [with reference to the W.H.O. Second International Low Molecular Weight Heparin Reference Standard]) per 0.1 mL Water for Injection.

The Enoxaparin Sodium Injection prefilled syringes and graduated prefilled syringes are preservative-free and intended for use only as a single-dose injection [see Dosage and Administration (2) and How Supplied (16)].

Enoxaparin Sodium Injection

40 mg/0.4 mL

NDC 0548-5632-00

Rx ONLY

FOR SUBCUTANEOUS INJECTION

10 x 40 mg Single Dose Syringes with Automatic Safety Device

Manufactured for Amerinet Choice by

AMPHASTAR PHARMACEUTICALS, INC.

Rancho Cucamonga, CA 91730, U.S.A.

Made in U.S.A.

© 2012

Enoxaparin Sodium Injection

60 mg/0.6 mL

NDC 0548-5633-00

Rx ONLY

FOR SUBCUTANEOUS INJECTION

10 x 60 mg Single Dose Syringes with Automatic Safety Device

Manufactured for Amerinet Choice by

AMPHASTAR PHARMACEUTICALS, INC.

Rancho Cucamonga, CA 91730, U.S.A.

Made in U.S.A.

© 2012

Manufactured for Amerinet Choice by

AMPHASTAR PHARMACEUTICALS, INC.

Rancho Cucamonga, CA 91730, U.S.A.

Remove syringe by peeling lid completely off. Then gently lift straight up by grasping middle of syringe. Do not remove syringe by pulling on plunger. See www.amphastar.com

Enoxaparin Sodium Injection

60 mg/0.6 mL

Each 0.6 mL contains 60 mg of enoxaparin sodium derived from porcine mucosa in Water for Injection. See insert for directions for use.

FOR SUBCUTANEOUS INJECTION

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [See USP Controlled Room Temperature].

WARNING: KEEP OUT OF REACH OF CHILDREN

Each 0.025 mL graduation equals 2.5 mg Enoxaparin Sodium Injection

RX ONLY

8856336C 11-12

Stock No. 5633

NDC 0548-5633-00

1 Single Dose Prefilled Syringe with Automatic Safety Device

One 0.6 mL Syringe

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.